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Expert Opinion on Biological Therapy Jul 2008Currently G-CSFs such as filgrastim (Neupogen, Amgen, Inc.) and pegfilgrastim (Neulasta, Amgen, Inc.) are widely used to reduce chemotherapy-induced neutropenia.... (Review)
Review
BACKGROUND
Currently G-CSFs such as filgrastim (Neupogen, Amgen, Inc.) and pegfilgrastim (Neulasta, Amgen, Inc.) are widely used to reduce chemotherapy-induced neutropenia. Pegfilgrastim is a novel recombinant human G-CSF and its unique neutrophil-mediated clearance allows it to be administered once per chemotherapy cycle.
OBJECTIVE
To address the pharmacology of pegfilgrastim and provide an overview of its current clinical use in cancer chemotherapy.
METHODS
Review and summary of publications on pegfilgrastim indexed in the PubMed electronic database.
RESULTS/CONCLUSION
The efficacy of pegfilgrastim is similar to or greater than that of filgrastim and an important advantage of pegfilgrastim is its schedule of administration that may be associated with greater treatment compliance and improved patient quality of life. Ongoing clinical trials continue to explore further potential uses for pegfilgrastim.
Topics: Animals; Clinical Trials as Topic; Dose-Response Relationship, Drug; Drug Design; Filgrastim; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Mobilization; Humans; Neoplasms; Neutropenia; Neutrophils; Placebos; Polyethylene Glycols; Quality of Life; Randomized Controlled Trials as Topic; Recombinant Proteins
PubMed: 18549328
DOI: 10.1517/14712598.8.7.993 -
Supportive Care in Cancer : Official... Nov 2017Chemotherapy-induced febrile neutropenia (FN) causes treatment delays and interruptions and can have fatal consequences. Current guidelines provide recommendations on... (Review)
Review
PURPOSE
Chemotherapy-induced febrile neutropenia (FN) causes treatment delays and interruptions and can have fatal consequences. Current guidelines provide recommendations on granulocyte colony-stimulating factors (G-CSF) for prevention of FN, but guidance is unclear regarding use of short- vs long-acting G-CSF (e.g., filgrastim vs pegfilgrastim/lipegfilgrastim, respectively). An international panel of experts convened to develop guidance on appropriate use of pegfilgrastim for prevention of chemotherapy-induced FN.
METHODS
Guidance recommendations were developed following a literature review, survey, evaluation of current practice, and an expert meeting. Consensus was established using an anonymous Delphi-based approach.
RESULTS
Guidance recommendations for prevention of treatment-associated FN were as follows: for treatment with curative intent, maintenance of dose intensity using G-CSF to prevent dose delays/reduction should be standard of care; for treatment-associated FN risk ≥ 20%, short-acting G-CSF/pegfilgrastim should be given from cycle 1 onwards; and for treatment-associated FN risk < 20%, short-acting G-CSF/pegfilgrastim should be given if factors suggest overall risk (including treatment-related and patient-related risk factors) is ≥ 20%. It was agreed that pegfilgrastim and 11 days' filgrastim have similar efficacy and safety and that pegfilgrastim is preferred to < 11 days' filgrastim (and may be preferred to ≥ 11 days' filgrastim based on adherence and convenience); pegfilgrastim is not appropriate in weekly chemotherapy; in split-dose chemotherapy, pegfilgrastim is recommended 24 h after last chemotherapy dose; and during palliative chemotherapy, patient adherence and convenience may favor pegfilgrastim.
CONCLUSION
In this era of targeted therapies, additional trials with G-CSF are still required. These recommendations should be used with existing guidelines to optimize pegfilgrastim use in clinical practice.
Topics: Chemotherapy-Induced Febrile Neutropenia; Consensus; Female; Filgrastim; Humans; Male; Polyethylene Glycols
PubMed: 28842778
DOI: 10.1007/s00520-017-3842-1 -
Drugs 2002Neutropenia is a common and potentially dangerous adverse effect of cancer chemotherapy. It also often necessitates a reduction or delay in dose, thus compromising... (Review)
Review
Neutropenia is a common and potentially dangerous adverse effect of cancer chemotherapy. It also often necessitates a reduction or delay in dose, thus compromising efficacy. The human granulocyte colony-stimulating factor filgrastim has been proven to have a good safety profile and to be effective in accelerating neutrophil recovery and reducing the incidence of infections following myelosuppressive chemotherapy. However, its short serum half-life necessitates daily administration. Pegylated filgrastim (pegfilgrastim) was developed by attaching a polyethylene glycol moiety to the filgrastim protein. Pegfilgrastim binds to the same cell surface receptor on neutrophils and their precursors as filgrastim and stimulates the proliferation and differentiation of neutrophils through the same mechanism. However, because of the pegylation, it is minimally cleared by the kidneys and has a much longer serum half-life. Furthermore, its clearance is neutrophil dependent and thus 'self-regulated'. Pegfilgrastim is administered as a single subcutaneous injection per cycle of chemotherapy. In clinical trials it has been shown to be comparable in efficacy to filgrastim in decreasing the incidence of infection as manifested by febrile neutropenia following chemotherapy. Its safety profile and tolerability are similar to those of filgrastim.
Topics: Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; Filgrastim; Granulocyte Colony-Stimulating Factor; Humans; Incidence; Injections, Subcutaneous; Neoplasms; Neutropenia; Periodicity; Polyethylene Glycols; Recombinant Proteins; Treatment Outcome
PubMed: 12479597
DOI: 10.2165/00003495-200262001-00007 -
Critical Reviews in Oncology/hematology Jun 2010We investigated the incidences of febrile neutropenia (FN) and related complications in elderly (> or =65 years) breast cancer patients receiving chemotherapy supported... (Review)
Review
We investigated the incidences of febrile neutropenia (FN) and related complications in elderly (> or =65 years) breast cancer patients receiving chemotherapy supported by pegfilgrastim primary prophylaxis (PP; n=150) or current practice (CP) neutropenia management (n=104) in a subanalysis of NeuCuP (Neulasta) vs. current practice neutropenia management). Studies involving regimens with moderately high to high (> or =15%) FN risk were identified by literature review, and individual patient data were integrated for analysis. FN incidence was 6% (95% CI: 2, 10%) in the PP group and 24% (95% CI: 16, 32%) in the CP group. In cycle 1, incidences were 3 and 15%, respectively. FN-related hospitalisation incidence was 5% (PP group) and 15% (CP group), while dose reductions (>/=15%) occurred in 15 and 29% of patients. Pegfilgrastim provided effective PP in elderly patients, a population who may be vulnerable to chemotherapy-related FN and for whom current practice may not provide adequate protection.
Topics: Aged; Antineoplastic Agents; Breast Neoplasms; Female; Filgrastim; Granulocyte Colony-Stimulating Factor; Humans; Neutropenia; Polyethylene Glycols; Recombinant Proteins
PubMed: 19748281
DOI: 10.1016/j.critrevonc.2009.06.004 -
Journal of Oncology Practice Jul 2013Pegfilgrastim reduces the risk of febrile neutropenia (FN) and is indicated as primary prophylaxis when the risk of FN approaches 20% in each chemotherapy cycle. There... (Review)
Review
PURPOSE
Pegfilgrastim reduces the risk of febrile neutropenia (FN) and is indicated as primary prophylaxis when the risk of FN approaches 20% in each chemotherapy cycle. There have been few reports evaluating the appropriate use of pegfilgrastim in comparison with published guidelines. We sought to determine possible over-prescribing as a way to maintain quality and reduce cost.
METHODS
A retrospective medical record review was performed to determine whether pegfilgrastim was used appropriately in the primary prophylaxis of FN in chemotherapy regimens with less than 20% risk of FN. Patients were identified by means of administrative records, and data were collected from the electronic medical record at an academic cancer center outpatient clinic serving approximately 13,000 patients per year.
RESULTS
Two hundred ninety-two patients were identified, of whom 124 were initially evaluated and 88 were included. Thirty-three patients (37%) had no risk factors, and 20 (22%) had one risk factor that would justify pegfilgrastim use with low- or intermediate-risk regimens. The most common cancer diagnosis of patients with zero or one risk factor was lymphoma, and the most common regimens with overuse of pegfilgrastim were doxorubicin-bleomycin-vinblastine-dacarbazine (ABVD) and ritux-imab-cyclophosphamide-doxorubicin-vincristine-prednisone (R-CHOP). One hundred eighty-four pegfilgrastim doses (46%) were classified as avoidable. The cost to the health system for unnecessary drug use was $712,264 in 1 year.
CONCLUSION
At one institution, approximately one half of all primary prophylaxis pegfilgrastim was not indicated per published guidelines. This represents an excellent opportunity to change prescribing practices to reduce costs without harming patients.
Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy-Induced Febrile Neutropenia; Cost-Benefit Analysis; Drug Prescriptions; Female; Filgrastim; Granulocyte Colony-Stimulating Factor; Hospitals, University; Humans; Male; Middle Aged; Neoplasms; Outpatient Clinics, Hospital; Polyethylene Glycols; Practice Guidelines as Topic; Practice Patterns, Physicians'; Recombinant Proteins; Retrospective Studies; Risk Factors
PubMed: 23942922
DOI: 10.1200/JOP.2012.000662 -
Transfusion and Apheresis Science :... Jun 2008Granulocyte colony-stimulating factors (G-CSF) are established prerequisites for the mobilization of peripheral blood stem cells (PBSC). Pegylated filgrastim... (Review)
Review
Granulocyte colony-stimulating factors (G-CSF) are established prerequisites for the mobilization of peripheral blood stem cells (PBSC). Pegylated filgrastim (pegfilgrastim) has a substantially increased elimination half-life due to decreased serum clearance. A single-dose of pegfilgrastim is equivalent in enhancing neutrophil recovery after chemotherapy compared to daily filgrastim administrations. Several clinical trials also investigated chemotherapy plus single-dose pegfilgrastim in the mobilization of autologous PBSC in patients with lymphoma or myeloma. The results indicated similar efficacy compared to unconjugated G-CSF in terms of blood CD34+ cell count, stem cell yields as well as engraftment of after reinfusion. However, the number of patients in these trials were limited and there were non-randomized controls only. Furthermore, the mobilization of 12 mg pegfilgrastim was not superior over the 6 mg dose, and in one trial insufficient results were observed in heavily pretreated patients. In allogeneic stem cell donors a single-dose of 12 mg pegfilgrastim has been shown to induce a sufficient increase of blood CD34+ cells with a similar kinetics as known from conventional G-CSF. Adequate numbers of PBSC for transplantation could be harvested mostly by a single apheresis. Bone pain and headaches appeared to be more severe and about 90% of donors required analgetics. Additional concerns are due to spleen enlargement and hyperleukocytosis. Promising insights were reported from preclinical studies which revealed a modulating impact on both graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) effect after transplantation of pegfilgrastim mobilized PBSC. Further trials are needed which carefully evaluate the issues of donor safety, but also the impact on graft composition and recipients' outcome.
Topics: Blood Component Removal; Filgrastim; Graft Survival; Graft vs Host Disease; Graft vs Leukemia Effect; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cells; Humans; Lymphoma; Multiple Myeloma; Peripheral Blood Stem Cell Transplantation; Polyethylene Glycols; Recombinant Proteins; Transplantation, Autologous
PubMed: 18490197
DOI: 10.1016/j.transci.2008.04.007 -
Medical Oncology (Northwood, London,... Dec 2011Single-dose pegfilgrastim is commonly used for the prophylaxis of neutropenia in patients receiving myelotoxic chemotherapy. We report a case of a 69-year-old man who... (Review)
Review
Single-dose pegfilgrastim is commonly used for the prophylaxis of neutropenia in patients receiving myelotoxic chemotherapy. We report a case of a 69-year-old man who was treated with chemotherapy for small-cell lung cancer and mistakenly self-administered a 36 mg overdose of pegfilgrastim, a sixfold increase over the scheduled dose.
Topics: Aged; Drug Overdose; Filgrastim; Granulocyte Colony-Stimulating Factor; Humans; Male; Medication Errors; Polyethylene Glycols; Recombinant Proteins; Self Care
PubMed: 21107754
DOI: 10.1007/s12032-010-9751-5 -
Chemotherapy 2012Patients receiving cytotoxic chemotherapy are at risk for developing chemotherapy-induced neutropenia (CIN). Filgrastim, a recombinant granulocyte colony-stimulating... (Review)
Review
Patients receiving cytotoxic chemotherapy are at risk for developing chemotherapy-induced neutropenia (CIN). Filgrastim, a recombinant granulocyte colony-stimulating factor (G-CSF) that stimulates the proliferation, differentiation and function of neutrophils, is approved for the prevention of CIN. To eliminate the burden of daily filgrastim injection, pegfilgrastim, a long-acting form of filgrastim, was developed by covalently attaching a 20-kDa polyethylene glycol molecule to filgrastim to increase molecular size and thus reduce renal elimination. Consequently, neutrophil-mediated clearance is the primary mechanism for pegfilgrastim elimination. Therefore, after a single pegfilgrastim injection following chemotherapy treatment, pegfilgrastim concentration is sustained during neutropenia and decreases with neutrophil recovery. Pegfilgrastim has received marketing authorization approval from many regions to reduce the incidence of CIN based on the similar efficacy and safety of a single injection of 6 mg of pegfilgrastim administered once per chemotherapy cycle and 10 to 11 daily injections of filgrastim at 5 µg/kg. The efficient self-regulating clearance of pegfilgrastim allows administration once per chemotherapy cycle, thereby providing a more convenient treatment regimen than filgrastim.
Topics: Antineoplastic Agents; Filgrastim; Granulocyte Colony-Stimulating Factor; Half-Life; Humans; Neoplasms; Neutropenia; Polyethylene Glycols; Recombinant Proteins; Treatment Outcome
PubMed: 23296266
DOI: 10.1159/000345626 -
Seminars in Oncology Aug 2003Filgrastim (r-metHuG-CSF) was approved in the United States in 1991 for use in decreasing the incidence of infection, as manifested by febrile neutropenia, in patients... (Review)
Review
Filgrastim (r-metHuG-CSF) was approved in the United States in 1991 for use in decreasing the incidence of infection, as manifested by febrile neutropenia, in patients with nonmyeloid malignancies treated with myelosuppressive chemotherapy. Colony-stimulating factors such as filgrastim are a significant advance in the supportive care of patients with cancer. However, because of its short half-life, filgrastim requires daily dosing by injection to maintain its effects on the bone marrow. Pegfilgrastim (Neulasta; Amgen, Thousand Oaks, CA) is a longer-acting, self-regulating form of filgrastim created by the covalent linkage of a 20-kd polyethylene glycol molecule to the N-terminal of the filgrastim molecule. The molecular characteristics of pegfilgrastim result in a longer terminal half-life, making once-per-chemotherapy-cycle administration possible. The results from two randomized double-blind phase III clinical trials in patients with breast cancer treated with myelosuppressive chemotherapy showed that a single dose of pegfilgrastim provides neutrophil support comparable with that provided by an average of 11 daily injections of filgrastim. Pegfilgrastim has also been shown to be comparable to filgrastim in reducing neutropenic complications in patients treated with chemotherapy for lymphoma. Data from three clinical trials have been presented: a randomized controlled trial in elderly patients treated with CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone) for relapsed or refractory non-Hodgkin's lymphoma; a randomized controlled trial in patients treated with ESHAP (etoposide/methylprednisolone/cisplatin/cytarabine) for relapsed or refractory lymphoma; and a study in patients with newly diagnosed non-Hodgkin's lymphoma. The safety profile of pegfilgrastim is comparable to that of filgrastim in the clinical settings studied to date. The once-per-cycle administration of pegfilgrastim may improve patient quality of life because it is less disruptive to patients and caregivers, and increase adherence because no doses are missed, thus further advancing the management of chemotherapy-induced neutropenia and its consequences.
Topics: Antineoplastic Agents; Clinical Trials as Topic; Colony-Stimulating Factors; Filgrastim; Granulocyte Colony-Stimulating Factor; Humans; Neoplasms; Neutropenia; Polyethylene Glycols; Recombinant Proteins
PubMed: 14508717
DOI: 10.1016/s0093-7754(03)00314-2 -
Journal of Drugs in Dermatology : JDD Apr 2022Sweet syndrome, or acute febrile neutrophilic dermatosis, is a skin condition consisting of erythematous papules and plaques in association with fever, neutrophilia, and...
Sweet syndrome, or acute febrile neutrophilic dermatosis, is a skin condition consisting of erythematous papules and plaques in association with fever, neutrophilia, and a neutrophilic infiltrate that typically involves the papillary dermis. Although development is most commonly idiopathic, medications are also frequently associated with the eruption, notably, the granulocyte colony-stimulating factor (G-CSF), filgrastim. Pegylated G-CSF, despite similar activity, is not commonly reported, with only four published cases. We present a case of drug-induced sweet syndrome with unique histologic features (deep inflammatory infiltrate) in association with the usage of pegfilgrastim in the treatment of invasive ductal carcinoma of the breast. J Drugs Dermatol. 2022;21(4):422-424. doi:10.36849/JDD.4794.
Topics: Filgrastim; Granulocyte Colony-Stimulating Factor; Humans; Polyethylene Glycols; Sweet Syndrome
PubMed: 35389579
DOI: 10.36849/JDD.4794